Depression remains the most common of the disabling psychiatric illnesses. However, as we examine the expression of this disorder across the adult lifespan, it becomes increasingly obvious that depression is probably not one disorder but many. Thus, over the next five years, the MHCRC for Affective Disorders at the University of Pittsburgh will continue to encourage multiple approaches to the study of depression at all points along the adult age spectrum. Organizing all of these approaches is the hypothesis that depression involves a dysfunction of multiple, interrelated systems and not simply a change of mood. The attempt to understand these interrelationships creates bridges across investigations of therapeutics, regulatory systems, membrane abnormalities, and molecular biology. The Department of Psychiatry (WPIC), in collaboration with a variety of other departments within the School f Medicine and the Faculty of Arts and Sciences both at the University of Pittsburgh, at nearby Carnegie-Mellon University and at the research centers across the country, will continue to investigate the etiology, pathophysiology, course and treatment of affective disorders. The MHCRC provides the essential organizing structure and core support for our integrated, multidisciplinary program of research and research training. The MHCRC consists of two primary components: core support facilities and research programs. The cores required to support the next five years of research activities are: 1) the biological rhythms/psychobiology core, 2) the clinical psychopharmacology core, 3) the molecular biology and genetics core 4) the late-life mental disorder (affective disorder) core and 5) the methodology core. These five core support systems provide common facilities, technical expertise and scientific direction, integrating the work of a large number of research scientists. In addition, the MHCRC will permit continued seed funding of young investigators, the pairing of seasoned investigators with these young scientists and communication among the senior faculty interested in widely differing aspects of affective disorders. Clinical research programs, covering the entire adult age spectrum, are organized around the theme of regulatory disturbances, as viewed through a longitudinal perspective and as altered by treatment interventions. Basic research programs echo this theme as it can be explored at the molecular, cellular and organismic level in both animal and human studies.